Gonadotropins: Uses, common brands, and safety info

Gonads are the primary reproductive organs in the human body. For females, this is the ovaries, and for males, this is the testes. Gonadotropins are the hormones released by the anterior pituitary gland in your body in response to gonadotropin-releasing hormone (GnRH). Gonadotropins then act upon the reproductive organs to increase the production of sex hormones and the release of eggs and sperm. Gonadotropin drugs are hormone medications used in the treatment of infertility. The actions of gonadotropin drug treatment may induce ovulation, produce follicles, and increase sperm counts. There are other types of infertility treatments including in vitro fertilization (IVF) and Clomid (clomiphene).  Here we will discuss the different gonadotropin drugs, how they work, and their safety.

Other gonadotropins

• HCG (chorionic gonadotropin)

• Profasi (chorionic gonadotropin)

• Follistim AQ (follicle stimulating hormone)

• Follistim (follicle stimulating hormone)

• Repronex (menotropins)

• Pergonal (menotropins)

• Luveris (lutropin alfa)

• Fertinex (urofollitropin)

• Bravelle (urofollitropin)

What are gonadotropins?

Gonadotropins are hormones responsible for the stimulation of the human reproductive organs which affect fertility, or the ability to conceive a baby. 

The two primary gonadotropin hormones are follicle-stimulating hormone (FSH) and luteinizing hormone (LH). Gonadotropin medications may be synthetically made or may be isolated from a natural source. There are three primary types of gonadotropin fertility drugs: 1) Menotropins, or human menopausal gonadotropin, 2) Recombinant human follicle-stimulating hormone, and 3) Human chorionic gonadotropin. These are marketed under various brand names.

How do gonadotropins work?

Follicles are liquid-filled sacs in the ovary where eggs grow and develop. FSH is the hormone responsible for triggering the growth of the follicle. An oocyte is an immature egg that will mature and grow within the follicle. When the ovarian follicle reaches maturation, the egg is released into the fallopian tube where it has the potential to be fertilized by sperm. This release is caused by a surge in the secretion of LH. Gonadotropin drugs imitate the functions of FSH, LH, or both depending on the drug.

What are gonadotropins used for?

Infertility 

Infertility is a term used to describe an inability to get pregnant after as a defined period of time, typically one year or longer of unprotected sex. To become pregnant, a series of several steps must occur. The woman’s ovaries must release the egg, and then the egg must be fertilized with the sperm released by the man. A fertilized egg must then move into the uterus to become attached to the uterine wall, also referred to as implantation. If an egg fails to be fertilized, it is shed as a part of the menstrual cycle of the woman. Infertility results when there is a problem with one or more steps in this process. 

Other uses include:

• Follicle stimulation

• Male hypogonadism

• Ovulation induction

• Prepubertal cryptorchidism

Types of gonadotropins 

Human Menopausal Gonadotropin (HMG)

This category, also called menotropins, are made of naturally produced FSH and LH which has been isolated from the urine of post-menopausal women. Once a woman enters menopause, she begins to pass high amounts of these hormones in her urine, making them easier to isolate and collect. 

Examples of HMG therapies: Menopur, Repronex, Pergonal

Recombinant Human Follicle-Stimulating Hormone (rFSH)

This category of gonadotropins are composed of genetically synthesized FSH.

Examples of rFSH therapies: Gonal-f, Gonal-f RFF, Follistim

Human Chorionic Gonadotropin (HCG)

This category of treatment contains both FSH and LH, but primarily displays effects of LH. HCG is produced by the human placenta and found in the urine of pregnant women.

Examples of HCG therapies: Pregnyl, Ovidrel, Novarel

Who can take gonadotropins?

Can men take gonadotropins?

Yes, adult men can take gonadotropin drugs for the treatment of hypogonadism. This occurs when the testes produce little to no hormones. This can lead to low sperm count which affects fertility.

Can women take gonadotropins?

Yes, adult women can take gonadotropin drugs to produce follicles and induce ovulation. 

Can you take gonadotropins while pregnant or breastfeeding?

Gonadotropins are absolutely contraindicated in pregnancy. While they are used to help achieve pregnancy, once conception has occurred, further use could be fatal to the unborn fetus. Before each fertility treatment, a woman’s pregnancy status should be confirmed. Birth defects and spontaneous abortions are possible if you take gonadotropins once you are pregnant. Breastfeeding while taking gonadotropin treatment should be done with caution as there is limited data on safety.

Can children take gonadotropins?

Human chorionic gonadotropin is approved for treating prepubertal cryptorchidism in infant and young male children. This is a condition where one or both of the testes have not dropped to their proper position in the scrotum prior to puberty. This is the only indication for which gonadotropin therapy is appropriate in children.

Can seniors take gonadotropins?

While not directly contraindicated, there is very little safety data for gonadotropin therapy in older patients. In some instances, it has been proven unsafe, such as in patients with prostate cancer, those with liver disease, or those with renal impairment.

Are gonadotropins safe?

Recalls

• Innoveix Pharmaceuticals, Inc: Potential lack of sterility October 2019

• KRD Global Biotechnology, Inc: Lack of sterility assurance September 2019

Restrictions

Gonadotropin drugs are contraindicated and should not be used in patients who have shown prior hypersensitivity to gonadotropin drugs. 

Gonadotropin drugs, specifically hCG, can lead to fluid retention in the body. Patients with conditions that may be worsened with fluid retention such as asthma, heart disease, kidney disease, or seizure disorders should be cautious when using hCG. 

Patients with a history of blood clotting disorders should also exercise caution when using gonadotropins. Though it is not a common occurrence, gonadotropin drugs can increase the chance of thromboembolism, a condition where a blood clot forms in a deep vein and then breaks loose to move to other areas to cut off the blood supply. This can be life-threatening.

Gonadotropin drugs are contraindicated in patients with sex hormone-dependent cancers. This can include breast cancer, ovarian cancer, and endometrial cancer in women. It should not be used in men with prostate cancer. Caution should also be used in women with uterine fibroids or endometriosis. 

Females who have been diagnosed with primary ovarian failure are not candidates for fertility treatments that call for ovarian overstimulation. Women with pre-existing ovarian cysts or who suffer from polycystic ovary syndrome (PCOS) may not be candidates for gonadotropin therapy. There are other treatments which may be appropriate for these patients such as in vitro fertilization (IVF), artificial insemination, or other reproductive technology depending on the cause of infertility.

Patients with uncontrolled thyroid disease, thyroid tumors, or untreated adrenal insufficiency should not utilize gonadotropin fertility treatments. 

Fad diets utilizing hCG have been popular at times. There is no clinical evidence to support the use of hCG to treat obesity, and hCG should not be used that way. 

Are gonadotropins controlled substances?

Injectable HCG formulations are considered a schedule III controlled substance in 9 states in the U.S. (CA, CO, CT, MN, NV, NY, NC, PA, and RI). In other states, it is still a prescription drug, but not a controlled substance. Other gonadotropin therapies are not considered controlled substances.

Common gonadotropins side effects

Most common side effects:

• Injection site reactions

• Elevated ALT liver enzyme

• Pain

• Gastrointestinal disorders

• Abdominal pain, cramps, or distension

• Nausea

• Ovarian cysts

• Pelvic pain

• Vomiting

• Diarrhea

• Fatigue

• Headache

• Weight gain

• Acne

Less common but more severe reactions include:

• Ovarian hyperstimulation syndrome (OHSS)

• Multiple pregnancies

• Ectopic pregnancies

• Thromboembolism (blood clot)

• Anaphylactic allergic reaction

• Hemoperitoneum 

• Pulmonary complications

How much do gonadotropins cost?

Gonadotropin fertility treatments are not cheap medications, and their cost may be prohibitive to some. Insurance coverage of fertility medications is inconsistent, and most patients are left searching for the best out-of-pocket price. SingleCare is a great resource for saving on your prescription medications. Your savings will depend on your exact therapy and your pharmacy choice. For example, Gonal-f, an FSH treatment, averaged $1223 for one injection. SingleCare can save you over $200 bringing lowering the price to $1022 at participating pharmacies. Ovidrel, Pregnyl, and generic chorionic gonadotropin preparations may be more affordable. A single Ovidrel injection will cost on average about $292, but a SingleCare savings card can bring that price to as low as $197. Always ask your pharmacist to check the SingleCare discount to make sure you are getting the best price.